Influenza
Conditions
Keywords
Influenza in Long Term Care Setting, High dose Inactivated influenza vaccine, Standard dose inactivated influenza vaccine
Brief summary
The purpose of the study is to compare the performance of two currently available influenza (flu) vaccines. This study will try and determine if the high dose flu vaccine provides protection that is the same or better than that of regular dose flu vaccine. Both the regular dose and the high dose flu vaccines are approved by the FDA for use in older adults.
Detailed description
Influenza and pneumonia are the fifth leading cause of death in the United States, the leading cause of vaccine preventable death, and the leading cause of infection related deaths among nursing home residents(Nace, Drinka et al.2010). Each year, an estimated 36,000 individuals die from seasonal influenza and over 90% of these deaths occur among older adults, primarily the frail older adults residing in LTC settings(Fiore,Uyeki et al. 2010).Vaccination is the most effective means of preventing influenza (Nichol and Treanor 2006). Despite increasing success in immunizing LTC residents though, outbreaks continue to occur annually with case fatality rates ranging between 5-55% (Nace 2008). Older adults have a reduced response to influenza vaccination, in part due to age related immunosenescence (Keitel, Atmar et al. 1121; Skowronski, Tweed et al. 2008). It is widely recognized that more effective vaccine options are needed for frail older adults. One option is to increase the hemagglutinin (HA) dose in influenza vaccines in an effort to increase antibodies to hemagglutinin. To date, no studies have evaluated the effectiveness of the HDIV among LTC residents.
Interventions
BIOLOGICALHigh Dose Inactivated Influenza Vaccine
0.5 ml HDIV consisting of 180 mcg (60 mcg each strain) of influenza virus hemagglutinin
BIOLOGICALStandard Dose Inactivated Influenza Vaccine
0.5 ml of standard dose inactivated influenza vaccine consisting of a total of 45 mcg (15 mcg each strain) of influenza virus hemagglutinin
Sponsors
Sanofi Pasteur, a Sanofi Company
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Residents of one of the participating LTC sites * 65 years or older at the time of consent * require assistance in two or more Instrumental Activities of Daily Living and/or one or more Activities of Daily Living as identified by facility staff
Exclusion criteria
* Age less than 65 years * Life expectancy less than 6 months * History of allergic reaction to influenza vaccine, its components, or eggs * History of severe allergic reaction to latex * History of Guillian-Barre Syndrome * Actively undergoing chemotherapy * Actively undergoing radiation therapy * Use of prednisone (or other steroid) at prednisone-equivalent dosages of 10mg or higher within the past 14 days * Serious current immunosuppression or immunosuppression expected in the next 6 weeks * Any condition that, in the opinion of the investigator,might interfere with the evaluation of study objectives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | 30 days | The primary objective of this study is to determine the noninferiority of high- dose inactivated influenza vaccine (HDIV) versus standard dose inactivated influenza vaccine(SDIV)among residents of long term care(LTC)settings.Non-inferiority will be determined by comparing baseline and one month post vaccination HAI and MN titers using non-inferiority analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-inferiority and Immunoprotection Persistence at 6 Months | 6 months | Compare the immunogenicity via HAI and MN titers for HDIV and SDIV at 6 months in frail LTC residents |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled during the 2011-2012 and 2012-2013 influenza seasons
Pre-assignment details
A total of 205 participants from 15 community-based LTCFs who met all inclusion and none of the exclusion criteria were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| HD IIV Frail adults 65 years and older who received Fluzone High Dose intramuscularly | 89 |
| SD IIV Frail adults 65 years and older who received Fluzone Standard Dose intramuscularly | 98 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive allocation | 1 | 8 |
| Overall Study | Insufficient blood sample | 3 | 2 |
| Overall Study | Lost to Follow-up | 2 | 2 |
Baseline characteristics
| Characteristic | HD IIV | SD IIV | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 89 Participants | 98 Participants | 187 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 89 Participants | 96 Participants | 185 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 89 Participants | 96 Participants | 185 Participants |
| Region of Enrollment United States | 89 participants | 98 participants | 187 participants |
| Sex: Female, Male Female | 57 Participants | 71 Participants | 128 Participants |
| Sex: Female, Male Male | 32 Participants | 27 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 89 | 0 / 98 |
| serious Total, serious adverse events | 0 / 89 | 0 / 98 |
Outcome results
Primary
Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings
The primary objective of this study is to determine the noninferiority of high- dose inactivated influenza vaccine (HDIV) versus standard dose inactivated influenza vaccine(SDIV)among residents of long term care(LTC)settings.Non-inferiority will be determined by comparing baseline and one month post vaccination HAI and MN titers using non-inferiority analysis.
Time frame: 30 days
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/California/07/2009(H1N1)-2011-2012 Season | 78.2 titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/Victoria/210/2009(H3N2 | 26.2 titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | B/Brisbane/60/2008 | 25.6 titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/California/07/2009(H1N1)- 2012-2013 Season | 45.6 titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/Victoria/361/2011(H3N2) | 23.4 titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | B/Texas/6/2011 | 26.0 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/Victoria/361/2011(H3N2) | 14.2 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/California/07/2009(H1N1)-2011-2012 Season | 27.4 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/California/07/2009(H1N1)- 2012-2013 Season | 50.0 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/Victoria/210/2009(H3N2 | 10.2 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | B/Texas/6/2011 | 17.4 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | B/Brisbane/60/2008 | 14.3 titers |
p-value: 0.672t-test, 2 sided
p-value: 0.011t-test, 2 sided
p-value: 0.01t-test, 2 sided
p-value: 0.005t-test, 2 sided
p-value: 0.001t-test, 2 sided
p-value: 0.004t-test, 2 sided
Primary
Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings
The primary objective of this study is to determine the noninferiority of high- dose inactivated influenza vaccine (HDIV) versus standard dose inactivated influenza vaccine(SDIV)among residents of long term care(LTC)settings.Non-inferiority will be determined by comparing baseline and one month post vaccination HAI and MN titers using non-inferiority analysis.
Time frame: Day 0
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/California/07/2009(H1N1)2011-2012 Season | 17.1 titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/Victoria/210/2009(H3N2 | 8.9 titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | B/Brisbane/60/2008 | 15.3 titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/California/07/2009(H1N1) 2012-2013 Season | 23.6 titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/Victoria/361/2011(H3N2) | 7.2 titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | B/Texas/6/2011 | 7.9 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/Victoria/361/2011(H3N2) | 6.2 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/California/07/2009(H1N1)2011-2012 Season | 16.6 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/California/07/2009(H1N1) 2012-2013 Season | 32.3 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | A/Victoria/210/2009(H3N2 | 7.3 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | B/Texas/6/2011 | 9.1 titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority of High-dose Inactivated Influenza Vaccine(HDIV) Versus Standard Dose Inactivated Influenza Vaccine(SDIV) Among Residents of Long Term Care(LTC) Settings | B/Brisbane/60/2008 | 11.6 titers |
p-value: 0.917t-test, 2 sided
p-value: 0.36t-test, 2 sided
p-value: 0.248t-test, 2 sided
p-value: 0.178t-test, 2 sided
p-value: 0.152t-test, 2 sided
p-value: 0.285t-test, 2 sided
Secondary
Non-inferiority and Immunoprotection Persistence at 6 Months
Compare the immunogenicity via HAI and MN titers for HDIV and SDIV at 6 months in frail LTC residents
Time frame: 6 months
Population: The above numbers reflect the participants with data available at 6 months. Eleven subjects (five in the high dose and 6 in the standard dose groups) died of non-related causes. Some of the samples were insufficient or unable to be collected.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | A/California/07/2009(H1N1) 2011-2012 Season | 59.7 Titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | A/Victoria/210/2009(H3N2) | 22.3 Titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | B/Brisbane/60/2008 | 22.9 Titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | A/California/07/2009(H1N1) @012-2013 Season | 46.8 Titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | A/Victoria/361/2011(H3N2) | 24.7 Titers |
| High Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | B/Texas/6/2011 | 25.3 Titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | A/Victoria/361/2011(H3N2) | 13.4 Titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | A/California/07/2009(H1N1) 2011-2012 Season | 28.3 Titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | A/California/07/2009(H1N1) @012-2013 Season | 51.8 Titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | A/Victoria/210/2009(H3N2) | 9.4 Titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | B/Texas/6/2011 | 18.9 Titers |
| Standard Dose Inactivated Influenza Vaccine | Non-inferiority and Immunoprotection Persistence at 6 Months | B/Brisbane/60/2008 | 15.4 Titers |
p-value: 0.074t-test, 2 sided
p-value: 0.006t-test, 2 sided
p-value: 0.069t-test, 2 sided
p-value: 0.663t-test, 2 sided
p-value: 0.003t-test, 2 sided
p-value: 0.063t-test, 2 sided